EP1355648A2 - Inhibiteurs cycliques a disubstitution en position 1,2 de metalloproteases matricielles et de tnf alpha - Google Patents
Inhibiteurs cycliques a disubstitution en position 1,2 de metalloproteases matricielles et de tnf alphaInfo
- Publication number
- EP1355648A2 EP1355648A2 EP02714733A EP02714733A EP1355648A2 EP 1355648 A2 EP1355648 A2 EP 1355648A2 EP 02714733 A EP02714733 A EP 02714733A EP 02714733 A EP02714733 A EP 02714733A EP 1355648 A2 EP1355648 A2 EP 1355648A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- methyl
- phenyl
- alkyl
- crara1
- sep
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000003112 inhibitor Substances 0.000 title description 14
- 239000011159 matrix material Substances 0.000 title description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 60
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 47
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 44
- 150000003839 salts Chemical group 0.000 claims abstract description 37
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 174
- -1 (5-aryl-1 Chemical group 0.000 claims description 173
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 87
- 125000000217 alkyl group Chemical group 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 60
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 38
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- 125000002837 carbocyclic group Chemical group 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 29
- 108010003059 aggrecanase Proteins 0.000 claims description 28
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 26
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
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- 229910052794 bromium Inorganic materials 0.000 claims description 22
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 101150073096 NRAS gene Proteins 0.000 claims description 17
- 101150007570 nra-1 gene Proteins 0.000 claims description 16
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 14
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- 125000004419 alkynylene group Chemical group 0.000 claims description 10
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- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
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- 239000004305 biphenyl Substances 0.000 claims description 7
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
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- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 229910052702 rhenium Inorganic materials 0.000 claims description 6
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 5
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
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- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- BTVJTKWOCSGJDQ-UHFFFAOYSA-N 1-methylpiperidine-4-carboxamide Chemical compound CN1CCC(C(N)=O)CC1 BTVJTKWOCSGJDQ-UHFFFAOYSA-N 0.000 claims description 4
- IRXZANKMLZSWAG-UHFFFAOYSA-N 1-methylpyrrolidine-3-carboxamide Chemical compound CN1CCC(C(N)=O)C1 IRXZANKMLZSWAG-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 4
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- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
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- IKBGLOSAHCFRJG-UPVQGACJSA-N (2r,3s)-1-acetyl-n-hydroxy-2-[[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylmethyl]pyrrolidine-3-carboxamide Chemical compound CC(=O)N1CC[C@H](C(=O)NO)[C@@H]1CS(=O)(=O)C(C=C1)=CC=C1OCC1=CC(C)=NC2=CC=CC=C12 IKBGLOSAHCFRJG-UPVQGACJSA-N 0.000 claims description 2
- QYWWHNBHACMXEK-BRVRNLPISA-N (2r,3s)-n-hydroxy-2-[[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylmethyl]-1-(oxolane-2-carbonyl)pyrrolidine-3-carboxamide Chemical compound C([C@@H]([C@@H]1CS(=O)(=O)C2=CC=C(C=C2)OCC=2C=C(N=C3C=CC=CC3=2)C)C(=O)NO)CN1C(=O)C1CCCO1 QYWWHNBHACMXEK-BRVRNLPISA-N 0.000 claims description 2
- SJZJBCGHRHIZQR-HFKVKABFSA-N (2r,3s)-n-hydroxy-2-[[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylmethyl]-1-(oxolane-3-carbonyl)pyrrolidine-3-carboxamide Chemical compound C([C@@H]([C@@H]1CS(=O)(=O)C2=CC=C(C=C2)OCC=2C=C(N=C3C=CC=CC3=2)C)C(=O)NO)CN1C(=O)C1CCOC1 SJZJBCGHRHIZQR-HFKVKABFSA-N 0.000 claims description 2
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- HTTGXWWZNURROV-LADGPHEKSA-N (2s,3s)-n-hydroxy-1-methyl-2-[[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylmethyl]piperidine-3-carboxamide Chemical compound CN1CCC[C@H](C(=O)NO)[C@H]1CS(=O)(=O)C(C=C1)=CC=C1OCC1=CC(C)=NC2=CC=CC=C12 HTTGXWWZNURROV-LADGPHEKSA-N 0.000 claims description 2
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- XYBAHHZJRCWZJO-RDPSFJRHSA-N (3r,4s)-n-hydroxy-4-[[4-[(2-methylquinolin-4-yl)methoxy]phenyl]sulfonylmethyl]-1-prop-2-ynylpyrrolidine-3-carboxamide Chemical compound C=12C=CC=CC2=NC(C)=CC=1COC(C=C1)=CC=C1S(=O)(=O)C[C@@H]1CN(CC#C)C[C@@H]1C(=O)NO XYBAHHZJRCWZJO-RDPSFJRHSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
L'invention concerne des dérivés cycliques à disubstitution en position 1,2, représentés par la formule I, y compris leurs sels pharmaceutiquement acceptables. Le cycle B est un cycle non aromatique de 3 à 8 chaînons, qui comprend: des atomes de carbone, 0 ou 1 groupe carbonyle, 0 ou 1 double liaison, et entre 0 et 2 hétéroatomes du cycle, pouvant être O, N, NR2, et S(O)¿p?. Les autres variables sont telles que définies dans le corps de l'invention. Les dérivés considérés sont utiles comme inhibiteurs de métalloprotéase et de TNF alpha.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26095701P | 2001-01-11 | 2001-01-11 | |
| US260957P | 2001-01-11 | ||
| PCT/US2002/000760 WO2002055491A2 (fr) | 2001-01-11 | 2002-01-09 | Inhibiteurs cycliques a disubstitution en position 1,2 de metalloproteases matricielles et de tnf alpha |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1355648A2 true EP1355648A2 (fr) | 2003-10-29 |
Family
ID=22991353
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP02714733A Withdrawn EP1355648A2 (fr) | 2001-01-11 | 2002-01-09 | Inhibiteurs cycliques a disubstitution en position 1,2 de metalloproteases matricielles et de tnf alpha |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US6642255B2 (fr) |
| EP (1) | EP1355648A2 (fr) |
| AU (1) | AU2002246983A1 (fr) |
| CA (1) | CA2434044A1 (fr) |
| WO (1) | WO2002055491A2 (fr) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7319109B2 (en) * | 2002-11-22 | 2008-01-15 | Smith Kline Beecham Corporation | Farnesoid X receptor agonists |
| CA2511521C (fr) | 2002-12-30 | 2012-02-07 | Angiotech International Ag | Liberation de medicaments a partir d'une composition polymere a gelification rapide |
| US8088737B2 (en) | 2003-04-04 | 2012-01-03 | Incyte Corporation | Compositions, methods and kits relating to Her-2 cleavage |
| WO2004096139A2 (fr) | 2003-04-24 | 2004-11-11 | Incyte Corporation | Derives d'aza spiro alcane en tant qu'inhibiteurs de metalloproteases |
| MXPA06004191A (es) * | 2003-10-17 | 2007-01-19 | Incyte Corp | Hidroxamatos ciclicos sustituidos en la forma inhibidores de metaloproteinasas de matriz. |
| ES2338243T3 (es) * | 2004-03-22 | 2010-05-05 | Southern Research Institute | Inhibidores no peptidicos de metaloproteinasas matrices. |
| WO2009139817A2 (fr) | 2008-04-15 | 2009-11-19 | Sarcode Corporation | Produit pharmaceutique cristallin et ses procédés de préparation et d'utilisation |
| IT1393337B1 (it) | 2009-03-06 | 2012-04-20 | Italiana Sint Spa | Sintesi di (4as, 7as)-ottaidro-1h-pirrolo[3,4-b]piridina |
| JP6381445B2 (ja) * | 2011-12-08 | 2018-08-29 | リサーチ トライアングル インスティテュート | ニューロペプチドsレセプター(npsr)アンタゴニストの組成物および方法 |
| KR20170003688A (ko) | 2014-05-14 | 2017-01-09 | 더 리젠츠 오브 더 유니버시티 오브 콜로라도, 어 바디 코포레이트 | 단백질 탈아세틸화효소 억제제 및 이중 단백질 탈아세틸화효소-단백질 키나제 억제제로서의 헤테로사이클릭 하이드록삼산 및 그 이용 방법 |
| CN107383035B (zh) * | 2017-06-29 | 2019-06-25 | 上海合全药业股份有限公司 | 2-((1S3aR7aR)-5-叔丁氧羰基四氢呋喃并[3,4]哌啶-1)乙酸制法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT874830E (pt) | 1995-12-08 | 2003-06-30 | Agouron Pharma | Inibidor de metaloproteinases composicao farmaceutica contendo este inibidor e a utilizacao farmaceutica e metodo util para a sua preparacao |
| EP0780386B1 (fr) | 1995-12-20 | 2002-10-02 | F. Hoffmann-La Roche Ag | Inhibiteurs de métalloprotéases matricielles |
| TW448172B (en) | 1996-03-08 | 2001-08-01 | Pharmacia & Upjohn Co Llc | Novel hydroxamic acid derivatives useful for the treatment of diseases related to connective tissue degradation |
| EP0818442A3 (fr) | 1996-07-12 | 1998-12-30 | Pfizer Inc. | Dérivés cycliques de sulfones comme inhibiteurs de métalloprotéinase et de la production du facteur de nécrose des tumeurs |
| WO1998039316A1 (fr) | 1997-03-04 | 1998-09-11 | Monsanto Company | Composes n-hydroxy-4-sulfonyl-butanamide |
| EP1077974A1 (fr) | 1998-05-14 | 2001-02-28 | Du Pont Pharmaceuticals Company | Acides hydroxamiques a substitution aryle en tant qu'inhibiteurs de metalloproteinase |
-
2002
- 2002-01-09 CA CA002434044A patent/CA2434044A1/fr not_active Abandoned
- 2002-01-09 EP EP02714733A patent/EP1355648A2/fr not_active Withdrawn
- 2002-01-09 US US10/043,541 patent/US6642255B2/en not_active Expired - Lifetime
- 2002-01-09 AU AU2002246983A patent/AU2002246983A1/en not_active Abandoned
- 2002-01-09 WO PCT/US2002/000760 patent/WO2002055491A2/fr not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO02055491A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002055491A2 (fr) | 2002-07-18 |
| AU2002246983A1 (en) | 2002-07-24 |
| WO2002055491A3 (fr) | 2003-01-23 |
| US20030087890A1 (en) | 2003-05-08 |
| CA2434044A1 (fr) | 2002-07-18 |
| US6642255B2 (en) | 2003-11-04 |
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